Neonatal vitamin A supplementation to prevent mortality and morbidity in infancy

A recently published review set out to evaluate the effect of neonatal vitamin A supplementation on infant mortality, morbidity and early adverse effects. It involved a systematic review, meta-analysis, and meta-regression of randomised controlled trials. It considered randomised or quasi-randomised or cluster randomised, placebo controlled trials evaluating the effect of prophylactic, neonatal (<1 month) supplementation with synthetic vitamin A on mortality or morbidity within infancy (<1 year), and early adverse effects ( 7 days).

To investigate mortality during infancy, six trials were included, four in Asia and two in Africa. Two cluster randomised trials were included with design adjusted results. All trials were double blind with adequate allocation concealment, and loss to follow-up was below 10% in four trials. Three trials followed up participants up to 6 months of age. Two trials gave simultaneous maternal postpartum vitamin A supplementation ( 30% mothers in the intervention arm). In all trials, the cumulative dose of vitamin A was 50 000 IU, given as a single dose in five trials and as two doses in one trial. Information on prevalence of maternal night blindness was available in only three trials; of these, one recorded a prevalence <5%. Mortality during the neonatal period was pooled in three trials, two from Asia and one from Africa. Data from the African trial pertained to the first seven days of life only. In the factorial design study, mothers in the placebo group received supplementation (synthetic vitamin A or _ carotene) identical to the intervention group. Cause specific mortality pooled data was ascertained by verbal autopsy from four trials, two each from Africa and Asia.

Specific limitations included: all the trials were conducted in developing countries, which limits the generalisation of findings. There were limited data on high risk groups (maternal night blindness 5% and low birth weight infants). In the two cluster randomised trials, adverse effects were unadjusted for design effect. Duration of follow-up was variable. Multiple subgroup and meta-regression analyses were used, which increased the possibility of false positive results.

Conclusions

The authors found no evidence of a reduced risk of mortality during infancy (relative risk 0.92, 95% confidence interval 0.75 to 1.12, P=0.393 random effect; I2=54.1%) or of an increase in early adverse effects, including bulging fontanelle (1.16, 0.81 to 1.65, P=0.418; I2=65.3%). No variable emerged as a significant predictor of mortality, but data for important risk groups (high maternal night blindness prevalence and low birth weights) were restricted. Limited data (from one to four trials) did not indicate a reduced risk of mortality during the neonatal period (0.90, 0.75 to 1.08, P=0.270; I2=0%), cause specific mortality, common morbidities (diarrhoea and others), and admission to hospital. There was, however, evidence of an increased risk of acute respiratory infection and a reduced risk of clinic visits.

The authors conclude there is no convincing evidence of a reduced risk of mortality and possibly morbidity or of increased early adverse effects after neonatal supplementation with vitamin A. They consider no justification for initiating such supplementation as a public health intervention in developing countries for reducing infant mortality and morbidity.

'Rapid responses' to this paper, at BMJ online, raised some questions. These included whether there is a heterogeneity in the effect of Vitamin A in different populations AND THE NEED FOR further investigation to identify what sub-group of infants might benefit from neonatal supplementation. Access the full article and view 'rapid responses' at: http://www.bmj.com/cgi/content/full/338/mar27_1/b919